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NUCLEAR RESPIRATORY FACTOR-1 REGULATION BY PTEN SIGNALING
by
Yang Li
A Thesis Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(BIOCHEMISTRY AND MOLECULAR BIOLOGY)
August 2009
Copyright 2009 Yang Li

Based on many previous reports regarding cancer metabolism, it is believed that tumor cells need to obtain metabolic changes to maintain the malignant phenotype. Additionally, many PTEN-related studies revealed that PTEN mutation within the liver will eventually lead to liver cancer. The aim of this paper is to investigate the mechanism of how PTEN deletion gives rise to tumor phenotype and what kind of biological metabolism is suffering dysregulation due to PTEN mutation. In our results, mouse livers with PTEN mutation exhibited more lipid accumulation compared to PTEN wild type livers. PTEN mutant hepatocytes showed more mitochondrial biogenesis and enhanced respiration function than that in PTEN wild type hepatocytes. By performing a series of experiments, such as siRNA transfection, insulin-like growth factor-1 treatment, we concluded that NRF-1, which is an important transcription factor for mitochondrial biogenesis, is up-regulated by PTEN deletion through the activation of Phospo-AKT. This leads to more mitochondrial biogenesis and mitochondrial dysfunction, which may further cause tumor. This finding confirms previous studies and gives implication of the non-alcoholic fatty liver diseases (NAFLD) pathogenesis.

NUCLEAR RESPIRATORY FACTOR-1 REGULATION BY PTEN SIGNALING
by
Yang Li
A Thesis Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(BIOCHEMISTRY AND MOLECULAR BIOLOGY)
August 2009
Copyright 2009 Yang Li